Yoshihito Morimoto, Yoshiaki Sato, Katsuhiro Kato, Hidenori Yamamoto, Kentaro Suzuki, Kiyotaka Go, Yoshie Fukasawa, Naoki Ohashi, Yoshiyuki Takahashi, Taichi Kato
Nagoya University Graduate School of Medicine and Nagoya University Hospital. National Cerebral and Cardiovascular Center.
Japan
Journal of Molecular and Cellular Cardiology Plus
J Mol Cell Cardiol Plus 2026; 18:
DOI: 10.1016/j.jmccpl.2026.100867
Abstract
Rationale: Although plexiform lesion (PL) formation in severe pulmonary arterial hypertension (PAH) is a therapeutic target, the mechanisms underlying their formation have not been fully elucidated.
Objective: To identify candidate proteins involved in PL formation by examining differentially expressed proteins (DEPs) in PAH lesions.
Methods: Proteomic remodeling was assessed before and after the formation of PLs in a SU5416 combined with hypoxia (SuHx) rat model of severe PAH using laser-capture microdissection coupled with mass spectrometry. Unobstructed pulmonary arteries with medial hypertrophy (UMHPAs) and PLs from SuHx rats were subjected to qualitative and quantitative proteomics, revealing DEPs between these structures.
Results: We identified 718 proteins with 58 DEPs, of which 31 were upregulated in UMHPAs and 27 were upregulated in PLs. Immunostaining confirmed that DEPs detected in our proteomic analysis were differentially expressed between UMHPAs and PLs. Among them, we focused on heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) as a candidate protein that may be associated with PL formation because of its strong association with cell proliferation. Small interfering RNA knockdown of hnRNPA1 in hypoxia-treated pulmonary artery smooth muscle cells reduced pyruvate kinase M2 expression and decreased proliferative capacity.
Conclusions: Several DEPs associated with PL formation but with unclear relevance to pulmonary artery remodeling in PAH were discovered. Among these, hnRNPA1, which was not detected in transcriptome analysis and whole lung analysis, may be important in PL formation.
Category
Class I. Drug-induced and Toxin-induced Pulmonary Hypertension
Class III. Pulmonary Hypertension Associated with Alveolar Hypoxia
Animal Models of Pulmonary Vascular Disease and Therapy
Vascular Cell Biology and Mechanisms of Pulmonary Vascular Disease
Pulmonary Vascular Pathology
Age Focus: No Age-Related Focus
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes